Animal studies indicate that non-uniform precapillary occlusion with glass beads, fibrin-platelets, lipid emulsions or balloons can cause non-cardiac or permeability pulmonary edema with vascular leak occurring in perfused microvasculature. In the clinical counterpart, the adult respiratory distress syndrome (ARDS), non-uniform precapillary occlusion is hypothesized to occur by complement-mediated (C5a) leukocyte aggregation, fibrin-platelet microembolization and microembolization attributed to excessive fibronectin proteolysis. We have recently obtained evidence that enhanced fibrinogenolysis is specifically associated with ARDS in comparison to patients with underlying predispositions who did not develop this syndrome. Furthermore the fibrin(ogen) fragments circulating are not typical of plasmin cleavage products. These observations have led us to hypothesize that the excessive fibrinogenolysis associated with ARDS is mediated by another protease(s) which may be involved in the pathogenesis of the syndrome. To pursue this hypothesis we will characterize the circulating fibrinogen degradation products of ARDS by three methods: (1) immunoabsorption on antifibrinogen-agarose followed by elution and SDS polyacrylamide slab gel electrophoresis; (2) sucrose density gradient centrifugation followed by radioimmunoassay of fractions for the presence of fibrinogen fragment D; (3) molecular sieving of sera on agarose. In addition comparisons will be made of fibrinogen fragments from sera of ARDS patients with sera from patients with disseminated intravascular coagulation. Since the fragments in ARDS are atypical of plasmin action, comparisons of ARDS fibrinogen fragments will be made with fibrinolytic fragments generated by enzymes from human neutrophil and macrophage granules and with fibrinolytic fragments generated by individual human neutrophil enzymes, notably elastase. Finally isolated fibrinogen fragments from ARDS patients and/or the equivalent from rabbit fibrinogen will be placed intratracheally and infused intravenously into rabbits to begin to assess phlogistic properties of these atypical fibrinogen degradation products.